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Disposition and irreversible plasma protein binding of tolmetin in humans
Author(s) -
Hyneck Martha L,
Smith Philip C,
Munafo Alain,
McDonagh Antony F,
Benet Leslie Z
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.120
Subject(s) - glucuronide , chemistry , pharmacokinetics , urine , in vivo , pharmacology , plasma protein binding , plasma concentration , clinical pharmacology , biochemistry , medicine , biology , microbiology and biotechnology
The pharmacokinetics and irreversible plasma protein binding of tolmetin were studied in six healthy subjects after the administration of a single, 400 mg dose of tolmetin. With HPLC analysis, tolmetin, tolmetin glucuronide, and the isomers of tolmetin glucuronide, which result from intramolecular acyl migration in vivo, were detected in the plasma up to 4 hours after administration, whereas these conjugates were present in the urine up to 24 hours. Irreversible binding of tolmetin to plasma proteins occurred in all subjects. Irreversible binding exhibited a better correlation with exposure to tolmetin glucuronide ( r = 0.5618) and the isomers of tolmetin glucuronide ( r = 0.8200) than with exposure to tolmetin (−0.3635). This is consistent with the hypothesis that covalent binding occurs via the acyl glucuronide. Clinical Pharmacology and Therapeutics (1988) 44, 107–114; doi: 10.1038/clpt.1988.120